Effect of baicalein on reversal of multidrug resistance in MCF-7/MX cells in vitro and its mechanisms / 中国药理学通报

Aim To investigate the effect of baicalein on the reversal of multidrug resistance ( MDR) media-ted by breast cancer resistance protein ( BCRP) in hu-man breast cancer MCF-7/MX cells, and explore the possible mechanisms. Methods MTT assay was per-formed to determine the cytotoxicity of baicalein and susceptibility of chemotherapeutic drugs. The protein expression levels of BCRP, p-p38 MAPK and NF-κB p65 were determined by Western blot. Results MCF-7/MX cells were not only resistant to MX but cross-re-sistant to 5-FU and DDP, and the resistance index was 70. 45, 6. 68 and 21. 47, respectively. 2. 5, 5μmol· L-1 of baicalein could increase the sensitivity to above chemotherapeutic agents and decrease the expression levels of BCRP, p-p38 MAPK and NF-κB p65 in MCF-7/MX cells. Conclusion Baicalein can effec-tively reverse MDR of MCF-7/MX by down-regulating BCRP expression through p38/MAPK and NF-κB path-ways.

Baicalein inhibits monocrotaline-induced vascular wall thickening in rats with pulmonary hypertension / 中国病理生理杂志

AIM:To investigate the effects of baicalein on pulmonary arterial hypertension(PAH)induced by monocrotaline(MCT)in rats,and its molecular mechanism was further explored.METHODS: Male SD rats(n=28) were randomly divided into 4 groups: control group, MCT group, MCT+baicalein 50 mg/kg group and MCT +baicalein 100 mg/kg group.The PAH model was established by subcutaneous injection of MCT.After 2 weeks of modeling,the rats in baicalein treatment groups were gavaged baicalein 50 and 100 mg· kg -1· d-1for 14 d,the rats in control group were administered with saline.After 4 weeks of modeling,right ventricular systolic pressure(RVSP),right ventricular hypertro-phy index(RVHI)and right ventricular mass index(RVMI)were detected.Masson staining was used to detect the degree of lung fibrosis.The pathomorphological changes of the pulmonary vessels were observed by HE staining.Western blot was used to detect the expression of α-smooth muscle actin(α-SMA)in the lung tissue and the phosphorylation p 38,ERK and JNK in the artery.RESULTS:Compared with the control group,RVSP, RVHI and RVMI increased significantly in the MCT group(P<0.01).Pulmonary fibrosis and the thickening of pulmonary artery wall were observed.α-SMA was up-regulated and p38,ERK and JNK was activated significantly(P<0.01).Compared with the MCT group,baicalein(50 and 100 mg/kg)significantly decreased the RVSP,RVHI and RVMI(P<0.01).Lung fibrosis was reduced and the vas-cular wall thickening was decreased in baicalein-treated groups.Baicalein(50 and 100 mg/kg)inhibited the phosphoryla-tion of p38,ERK and JNK compared with the MCT group(P<0.01).CONCLUSION:Baicalein ameliorates MCT-in-duced PAH by the inhibition of pulmonary artery wall thickening at least partially via MAPK signaling pathway.

The surface biomarkers of sputum cells in coal mine workers and patients with pneumoconiosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the significance of intercellular adhesion molecule -1 (CD54 or ICAM-1), epidermal growth factor receptor (EGFR) and platelet-derived factor (PDGF) in sputum cells of workers exposed to dust and patients with pneumoconiosis for the early diagnosis of pneumoconiosis.</p><p><b>METHODS</b>The subjects included 62 workers exposed to dusts, 51 workers not exposed to dusts, 22 patients with pneumoconiosis and 10 healthy controls. The respiratory sputum technique was used to collect the sputum samples and the biomarkers (ICAM-1, EGFR and PDGF) of the sputum samples were detected with the sputum samples.</p><p><b>RESULTS</b>When the exposure group was compared with non-exposure group, there were no significant differences of surface biomarkers (ICAM-1, EGFR and PDGF) in sputum cells (neutrophil leucocytes, macrophages, lymphocytes and acidophilic/basophil leucocytes). As compared with other workers exposed to dusts, the surface CD54 and EGFR expression levels increased significantly and the surface PDGF expression level decreased significantly in workers exposed to dusts for 10 years (P<0.05). As compared with controls, the CD54 and EGFR expression levels of sputum cells increased significantly and the PDGF expression level of sputum cells decreased significantly in patients with pneumoconiosis at the stages of I and II + mI (P<0.05).</p><p><b>CONCLUSION</b>The expression levels of the surface CD54, EGFR and PDGF of sputum cells in workers exposed to dusts and patients with pneumoconiosis changed, which may be useful for early detecting pneumoconiosis.and patients is changed, which may be meaningful for early detection of pneumoconiosis.</p>

Involvement of Toll-like receptor in silica-induced tumor necrosis factor alpha release from human macrophage cell line / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To characterize the role of Toll-like receptor 4 (TLR4) in silica-induced production of tumor necrosis factor alpha (TNFalpha) from macrophage cell line.</p><p><b>METHODS</b>The human macrophage cell line THP-1 was incubated with silica suspension. Cell media were collected and TNFalpha levels in the supernatants measured with ELISA. To examine the involvement of TLR4 in silica-induced TNFalpha release, the neutralizing antibody (HTA125) against human TLR4 receptor was employed to pretreat THP-1 cells prior to silica treatment. Moreover, murine macrophages expressing wild type or mutated TLR4 were also treated with silica to verify the effect of TLR4 in silica-induced TNFalpha release.</p><p><b>RESULTS</b>Compared with the control group [(3.18 +/- 0.41) pg/ml], the TNFalpha release in cells exposed to 100 microg/ml silica for 4 h and 8 h [(4.71 +/- 0.84), (6.22 +/- 0.58) pg/ml, respectively] increased 1.48 and 1.96 fold, respectively. Pretreatment of THP-1 cells with 20 microg/ml HTA125 antibody significantly blocked silica-induced TNFalpha release by 27%. Furthermore, the TNFalpha content released from cells expressing mutated TLR4 reduced by 30% in compared with that from the cells expressing wild type TLR4 after silica stimulation.</p><p><b>CONCLUSION</b>TLR4 mediates silica-induced TNFalpha release from macrophages.</p>

Effects and significance of gas explosion on expression of NF-kappaB and ICAM1 in lung tissue of rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the expression of NF-kappaB and ICAM-1 in the gas explosion wounded lung of rats and the relationship.</p><p><b>METHODS</b>Digoxin labeled NF-kappaB was used as probe. In situ hybridization was performed to detect the NF-kappaB mRNA. Immunohistochemistry was used to detect the expression of NF-kappaB and ICAM-1.</p><p><b>RESULTS</b>The levels of NF-kappaB mRNA, the expression of NF-kappaB and ICAM-1 in the wounded rats were significantly increased and reached their peak two hours after injury. Pathology of lung tissue showed that some crachea epithelium mucosae were desquamated; congestion, edema of trachea wall and infiltration of neutrophilic granulocytes were found; hemorrhage, edema and infiltration of lots of inflammatory cells were present in alveolus cells. Electron microscope showed that type I, especially type II alveolus epithelia had degeneration and desquamation.</p><p><b>CONCLUSION</b>The injury of gas explosion can activate NF-kappaB, which has close correlation with the acute injury to lung.</p>

A study on relationship between rat brain tissues hurts of the gas explosion and the expression of protein kinase CamRNA and c-fos gene / 中华劳动卫生职业病杂志

<p><b>OBJECTIVES</b>To explore relationship between rat brain tissues hurts of gas explosion and the expression of Protein Kinase C alpha mRNA.</p><p><b>METHODS</b>Build up rat hurt model of gas explosion. In Situ Hybridization (IDH) technique was used to test Protein Kinase C alpha mRNA. Immunohistochemical Assays (IHA) was used to determine c-fos gene protein.</p><p><b>RESULTS</b>Only a little a mount expression of PKC alpha mRNA and c-fos of the control group was detected. The expression of the cerebral cortex and hippocampus of PKC alpha mRNA 24 h, 48 h and the 48 h increased obviously, and the 48 h reached the peak of expression; (t = 4.12 P < 0.01). The expression of c-fos protein of the cerebral cortex and hippocampus started to increase obviously at 0.5 h and the 4 h reached the peak, then the strength lowered gradually and the expression level came back normal level on fifth day.</p><p><b>CONCLUSION</b>The anoxia of brain tissues due to the gas explosion may promote the expression of PKCamRNA, and PKCamRNA could regulate the expression of the gene of c-fos. Both PKCamRNA and the gene of c-fos are involved in harmful processes to the nerve cells.</p>